| Augmentation of intraluminal microvessel formation to facilitate guide wire crossing in chronic total occlusions -> Monitor Keywords |
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Augmentation of intraluminal microvessel formation to facilitate guide wire crossing in chronic total occlusionsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, Matrices, Synthetic PolymerAugmentation of intraluminal microvessel formation to facilitate guide wire crossing in chronic total occlusions description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070154555, Augmentation of intraluminal microvessel formation to facilitate guide wire crossing in chronic total occlusions. Brief Patent Description - Full Patent Description - Patent Application Claims
RELATED APPLICATIONS [0001] This application claims priority from U.S. Provisional Patent Application No. 60/632,267 filed Dec. 2, 2004, and this application is a continuation-in-part application of international patent application No. PCT/CA2005/001838 filed Dec. 2, 2005 and published under WO 2006/058434 on Jun. 8, 2006. The content of both of these prior applications is incorporated by reference into this application. FIELD OF THE INVENTION [0002] The present invention relates to percutaneous interventions of occluded vessels, e.g., arteries by augmenting intraluminal microvessel formation by local pro-angiogenic therapies. BACKGROUND OF THE INVENTION [0003] Coronary artery disease remains the leading cause of mortality in the western world. Chronic total occlusions (CTO), defined as occlusions of more than a month old, are very common in patients undergoing diagnostic coronary artery catheterisation with up to 20% of patients reported to have one or more CTO (1). This includes a large number of patients that have not actually had a myocardial infarction. Successful revascularization of CTO significantly improves angina in symptomatic patients (2, 3) and more recent data demonstrate improvement in left ventricular function (4-7), and even in reduction of mortality (8-10). Currently there are two possible therapeutic strategies for CTO revascularization: coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI) (angioplasty or stenting). Successful angioplasty requires that the operator place a small (360 .mu.m diameter) guide-wire through the tissue obstructing the lumen in a CTO in order to reach the distal arterial lumen. The technical difficulty of performing PCI in CTO, primarily because of inability to cross CTO with a guide wire, is reflected in the low rates of PCI for CTO (accounts for <8% of all PCI), despite the benefits of a positive outcome (11). Since PCI have severe limitations in this patient subset, clinicians frequently decide to refer these patients for CABG or persist with (often ineffective) medical therapy. The presence of one or more CTO of vessels supplying viable myocardium remains one of the most common reasons for referral for CABG rather than attempting PCI (12). [0004] The definition of a CTO is based on an angiographic appearance of complete absence of contrast reagent in a segment of an epicardial coronary artery. The distal artery beyond the CTO may not be visible or may be perfused by anterograde collaterals that are outside of the vessel lumen (termed "bridging collaterals") or by retrograde collaterals that originate from adjacent coronary vessels. Procedural success rates in stenotic (but non-occluded) coronary artery lesions are in excess of 95%. However, procedural success rates for CTO are only in the 60 to 70% range (3, 13, 14), with only modest improvement over the 50-60% success rates in the 1980's (23, 24), despite some improvements in angioplasty technology (25, 26). This current success rate for CTO is probably an overestimation in the sense that the majority of CTO are probably never even attempted due to expected failure. [0005] Inability to cross the CTO with a guide-wire is responsible for upwards of 75% of PCI failures (14, 15). In a minority of cases, the balloon or stent cannot cross the lesion despite successful guide-wire crossing. Despite its common occurrence, there is surprisingly little information about the pathophysiology of CTO, and why some CTO can be crossed while others are unsuccessful. [0006] The initial acute event leading to the development of a CTO is a ruptured atherosclerotic plaque with bidirectional thrombus formation. The thrombus and lipid-rich cholesterol esters are gradually replaced over time by the formation of collagen and calcium deposits (16, 17). This fibrous tissue is particularly dense at the proximal and distal ends of the lesion, which typically are the most resistant areas of the CTO for guide-wire crossing. Proteoglycans are also important components of the CTO within the first year (16). In later stages, the lesion becomes more calcified (16, 17). Despite the angiographic appearance of a CTO, microvessels are quite common in CTO (>75%), regardless of occlusion duration (FIG. 1) (16). [0007] There are three types of microvessel formation in arteries with advanced atherosclerotic lesions. The first pattern occurs in the vasa vasorum, which are the fine network of microvessels in the adventitia and outer media. These vessels proliferate in atherosclerosis and in response to vascular injury such as angioplasty and stenting (18-20). Hypoxia in the outer levels of the vessel wall appears to act as an important stimulus (36). Occasionally in CTO, these adventitial blood vessels are well developed and can be recognized as "bridging collaterals". Second, neovascularization can develop within occlusive intimal plaques, predominantly in response to chronic inflammation (21). Plaque neovascularization has been associated with progression of experimental atheromas in various animal models (22-25). The localization of plaque vessels in so-called "hot spots" in the shoulders of atheromas may predispose these plaques to rupture and acute coronary events (26, 27). The third type is the pattern of microvessel formation (known as "recanalization") that occurs as part of the organization phase in CTO in which thrombus is replaced by fibrous tissue. These microvessels generally range in size from 100-200 .mu.m but can be as large as 500 .mu.m (21). In contrast to the vasa vasorum which run in radial directions, these intimal microvessels run within and parallel to the thrombosed parent vessel (28). [0008] Knowledge of thrombus organization comes largely from the study of veins. This process resembles the pattern of wound healing (29). Initially, the freshly-formed thrombus contains platelets and erythrocytes within a fibrin mesh, which is followed by invasion of acute inflammatory cells (44). Neutrophils predominate at first but are later replaced with mononuclear cells. (30, 31). Endothelial cells also invade the fibrin lattice and form tube-like structures and microvessels within the organizing thrombi (29, 32). [0009] Relatively little is known about the process of microvessel formation in arterial thrombi. It cannot be assumed that the processes are identical in veins and arteries. Arterial thrombi recanalize less frequently and to a lesser extent than venous thrombi (33). The behavior of venous cells can differ substantially from their arterial counterparts (34, 35). Microvessels have been reported in 2-week-old mural thrombi in porcine aortas, which were attributed to mononuclear blood cells originating within the thrombus, with no apparent contribution from cells native to the vessel wall (36) or from invasion of vasa vasorum from the vessel wall (37, 387). Inflammation may also play a role since high concentrations of macrophages have been detected in regions of recanalization in spontaneous human thrombi and in experimental animal arterial thrombi (31, 39). The local ECM environment is probably an additional important modifier, with specific matrix components exerting either a pro-angiogenic (hyaluronan (40, 41), fibronectin (42, 43), perlecan (44-46), versican (47)), or anti-angiogenic (type I collagen (40, 48) decorin (49, 50)) effects. [0010] We have observed the presence of a variable number of microvessels in CTO. These preliminary observations suggest the possibility that these microvessels assist in successful CTO guide-wire crossings (see below). Microvessels have also been observed in a limited number of human coronary CTO studies (16), which has led us to the concept that intraluminal vascularization, and its effects on structural and mechanical properties of lesion, may substantially facilitate CTO guide-wire crossing rates. This can be studied using imaging techniques including magnetic resonance imaging (MRI) and 3D micro computed tomography (micro CT). SUMMARY OF THE INVENTION [0011] In accordance with the present invention, an approach to improve the current probability of a successful guidewire crossing of an occlusion in a mammalian vessel is described. Usually, a vessel is prepared so as to be capable of crossing of an occlusion situated therein by a guidewire of an intraluminal device, e.g. the guidewire of a balloon angioplasty catheter. Typically, the occlusion is a chronic total occlusion and vessel is a human artery, frequently located in the heart. [0012] In accordance with the invention, the occlusion is prepared for crossing by inducing angiogenesis therein. [0013] According to one aspect, the invention is a method of crossing a chronic total occlusion of a human. The method includes (i) inducing angiogenesis in the occlusion; and (ii) crossing the occlusion. [0014] Often, the invention involves (a) delivering an angiogenic agent to the occlusion site; (b) waiting a period of time sufficient to increase susceptibility of the occlusion to crossing through angiogenesis; and (c) crossing the occlusion. The agent can be delivered systemically. The agent is more typically delivered percutaneously directly to the site of the occlusion. [0015] In addition to inducing angiogenesis in an occlusion, other steps may be incorporated into the invention in preparing an occlusion for crossing, as exemplified throughout this specification. [0016] A potential advantage of the invention is an effective increase in intraluminal microvessel formation in a way that facilitates guide wire crossing and improves procedural success rates, without causing adverse effects to the vessel wall. [0017] The present invention is directed to a method of treating chronically occluded animals tubes such as fallopian tubes, ureters, and bile ducts. [0018] In a specific embodiment, the invention is a method for treating chronically occluded animal tubes and cavities. The first step in the method is administering a therapeutic effective amount of a pro-angiogenic substance(s) to an occluding atherosclerotic plaque. The substance(s) is delivered directly to a location adjacent the plaque to be brought into contact therewith, or in some embodiments, the substance(s) is delivered systemically, ultimately to be brought to the plaque. A combination of delivery methods is contemplated. There follows a pre-angioplasty waiting period prior to crossing the plaque with an angioplasty guide wire. This waiting period (1 day to 8 weeks, more likely between 2 days and 7 weeks, or 3 days and 6 weeks, or 4 days and 5 weeks, or 5 days and 4 weeks, or between about 1 and 3 weeks, often about 2 weeks) is required for the new microvessel formation. Following the waiting period, the occlusive plaque is crossed with an angioplasty guide wire. [0019] In another aspect, the invention is a method of preparing a vessel for crossing of an occlusion situated therein that includes delivering an angiogenic agent to the occlusion site. Delivering the angiogenic agent can include inserting a delivery device containing the agent directly into the vessel for deposition therein. In a particular aspect, the device includes a catheter, and delivering the agent to the occlusion site includes conveying the agent the vessel through the catheter. The distal end of the catheter can be brought within 10 cm of the occlusion prior to conveying the agent to the site through the catheter. The distal end, i.e., the delivery end of the catheter from which the agent emerges into the vessel is often brought into closer proximity of the target site, within 5 cm, or within 4 cm, or within 3 cm or even within 2 cm of the site. Delivering the agent to the occlusion site often includes bringing the agent into direct contact with the occlusion. [0020] Delivering the angiogenic agent can include lodging a device within the vessel in the proximity of the occlusion, the device being loaded with the agent. The agent is released from the device over an extended period of time, say up to about two hours, or between 20 minutes and 90 minutes or between 40 minutes and 60 minutes. Continue reading about Augmentation of intraluminal microvessel formation to facilitate guide wire crossing in chronic total occlusions... Full patent description for Augmentation of intraluminal microvessel formation to facilitate guide wire crossing in chronic total occlusions Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Augmentation of intraluminal microvessel formation to facilitate guide wire crossing in chronic total occlusions patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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